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15th
World Congress Clinical Nutrition
19th
– 22nd September 2010 El Sokhna Resort - Egypt
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Copyright © 2010.
WCCN2010.COM
All rights reserved |
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Timing nutrition makes the
difference concerning body weight
and survival
Sampling requirements for a
7-day/24-hour circadian endocrine
stress-strain test for nutritionists
interested in a premetabolic
syndrome. Historical
background by Paul Rosch
Franz Halberg1, Ning
Cegielski2, Germaine
Cornelissen1, Elias Ilyia2,
Paul Rosch3, Dewayne
Hillman1, Othild
Schwartzkopff1, R.B.
Singh4, Miguel Revilla5,
Maroun El-Khoury2, Fabien
De Meester6
1Halberg Chronobiology
Center, University of Minnesota,
Minneapolis, MN, USA
2DiagnosTechs, Kent, WA,
USA
3New York Medical
College, Yonkers, NY
4Halberg Hospital &
Research Inst, Centre of Nutr &Heart
Res, Moradabad, India
5University of
Valladolid, Spain
6TsimTsoum Institute,
Krakow, Poland
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We here aim at complementing and
where possible replacing the single
venipuncture-based diagnostic panel
of the current clinical-chemical
laboratory and substituting for the
blood pressure (BP) cuff (a manual
sphygmomanometer) in the examination
office, a sequence of saliva samples
along the scales of hours and years
for assessing circadian and
infradian endocrine and metabolic
rhythms, aligned with a
chronobiologically interpreted first
7-day/24-hour and, where indicated,
much longer chronobiologically-interpreted
BP and heart rate (HR) monitoring,
C-ABPM. C-ABPM has already served
for benetensive, transtensive and
maletensive load assessment in
feasibility tests (1-4), but the
application with endocrine and
metabolic tests is as yet only a
challenge and the elucidation of
endocrine sampling requirements is
our task herein.
We assume that William Osler's wear
(stress) and tear (strain) is best
assessed as one goes, preferably
during intact wear, to detect the
danger of a tear and to prevent it,
figuratively if not literally. In
the sense of Hooke's law of
elasticity extended as adjustability
to adrenocortical responses by Selye
(5, 6) and to our magnetic
environment near and far by measures
considered by Rosch (7), we
investigate requirements for a
circadian strain test consisting of
the assessment of endocrine
alterations in circadian MESOR,
amplitude and acrophase aligned with
vascular variability anomalies,
VVAs. When VVAs persist for several
7-day spans, they become vascular
variability disorders, VVDs, with a
very high risk of hard events (3).
In this context, we asked how many
days of 4-hourly around-the-clock
samples were needed for an objective
assessment of circadian rhythms in
salivary cortisol (C), DHEA (D),
melatonin (M) and testosterone,
estradiol and aldosterone, hormones
reflecting the circadian system by
their differently prominent rhythm
characteristics. Eventually, a test
of the endocrines, steroids in
particular, is preferably done
concomitantly with a first 7-day
half-hourly around-the-clock profile
of a C-ABPM record for as-one-goes
performance and strain assessment
with, as the case may be, VVA
detection (3, 4) and alignment with
wear and tear status (4) for use by
scholars in nutrition, among others
interested in infradian, notably
circannual interactions with
circadians (8, 9).
Procedure and Results. We analyzed a
>4-month-long record of 4-hourly
endocrine determinations covering ~2
months that were desynchronized from
the 24-hour societal schedule in
terms of salivary C, D and M as well
as systolic (S) and diastolic (D) BP
and HR, and another span of ~2
months wherein there was full
month-long resynchronization with
society's 24-hour schedule of C, D
and M, replicated for SBP, DBP and
HR (8). Saliva samples from a seleno-sensitive
woman, JF, 62 years of age, were
analyzed for this purpose by
chronobiologic serial sections with
resolutions differing by the use of
intervals of 1, 2, 3, 4 and 7 days.
The fit of the 24-hour cosine curve
by cosinor and serial sections to
737 determinations of each C, D and
M allowed rejection of the
zero-circadian amplitude (no-rhythm)
assumption at or near the 5% level
in intervals of 7 days in nearly all
intervals (99% of the 133-day
study). With intervals of 4 days,
rhythm detection occurred in 85% of
the intervals, Table 1 and Figure 1.
Even with intervals of only 2 days
was rhythm detection greater than
90% for M and >45% for C and D. Only
with 1-day intervals was rhythm
detection more problematic. But, of
course, denser sampling improves
resolution greatly, as demonstrated
for cortisol in blood in Figure 2
(9).
In the case of salivary
testosterone, estradiol and
aldosterone, a circadian rhythm
could not be consistently
demonstrated with intervals of 7
days, the zero-amplitude assumption
being rejected only in part of JF's
available record for these hormones
(N=162/hormone), as seen in Figure 3
for the two sex hormones. Without
extrapolating beyond the subject
investigated, but against the
background of a larger study on
blood (9), a 1-week saliva
collection at 4-hour intervals is
recommended only for M, C and D for
a glocal estimation of circadian
rhythmicity in both the synchronized
and the desynchronized state by
analyses both of the series covering
the week as a whole (globally) and
further on a daily basis (locally).
Aligning M, C and D series with
concomitantly monitored BP and HR
may be a powerful test to examine
any endocrine involvement in dealing
with loads from problems in
nutrition. The critical evidence for
the importance of timing nutrition
insofar as a calorie is differently
handled in various circadian stages
stemming from both the laboratory
and the clinic has been reviewed,
Figure 4 (10), and the effect on
body weight has been confirmed (11).
Since the internal timing of the
endocrines differs on
"breakfast-only" from that on
"dinner-only", with cortisol timing
changing by much less than certain
other hormones with the switch of
the timing of a single meal.
Nutritionists interested in
exploiting the timing of food may
study sampling requirements for
hormones other than those here
investigated (12).
A chronobiologic test based only on
BP assessment and, in the sense of
this abstract, a strain test has
already served to separate the
procedure here recommended from the
cornucopia of "stress tests" that
are qualified neither by minimal
sampling requirements nor by
circadian stage (13). The
chronobiologic interpretation of BP
and HR as well as of the endocrines
sets this strain test apart from
stress tests (13; cf. 10).
1. Halberg F, Cornélissen G, Spector
NH, Sonkowsky RP, Otsuka K, Baciu I,
Hriscu M, Schwartzkopff O, Bakken
EE. Stress/strain/life revisited.
Quantification by blood pressure
chronomics: benetensive,
transtensive or maletensive chrono-vasculo-neuro-immuno-modulation.
Biomedicine & Pharmacotherapy 2003;
57 (Suppl 1): 136s-163s.
2. Maschke C, Harder J, Cornélissen
G, Hecht K, Otsuka K, Halberg F.
Chronoecoepidemiology of "strain":
infradian chronomics of urinary
cortisol and catecholamines during
nightly exposure to noise.
Biomedicine & Pharmacotherapy 2003;
57 (Suppl 1): 126s-135s.
3. Halberg F, Cornélissen G, Otsuka
K, Siegelova J, Fiser B, Dusek J,
Homolka P, Sanchez de la Peña S,
Singh RB, BIOCOS project. Extended
consensus on need and means to
detect vascular variability
disorders (VVDs) and vascular
variability syndromes (VVSs).
Geronto-Geriatrics: Int J
Gerontology-ChronomeGeriatrics 2008;
11 (14): 119-146.
4. Halberg F, Cornélissen G, Halberg
Francine, Kessler T, Otsuka K.
Measuring mental strain by duration
of blood pressure overswing (CHAT):
case report. World Heart J, in
press.
5. Selye H. The general adaptation
syndrome and the diseases of
adaptation. J Clin Endocrinol 1946;
6: 117-230.
6. Selye H. Stress without Distress.
Philadelphia: Lippincott, 1974. 165
p.
7. Rosch PJ, Markov MS (eds.).
Bioelectromagnetic Medicine. New
York: Marcel Dekker; 2004. 850 pp.
8. Ilyia E, McCraty R, Halberg F,
Cornélissen G, Finley J, Thomas F,
Hillman D, Kino T, Chrousos G.
Frequency desynchronization of
salivary cortisol and DHEA in a
half-yearly recurrent adynamia
episode. Time Series (not spotcheck)
Evidence-Based Holistic Approach to
Health, 1st International Workshop
of the TsimTsoum Institute, Krakow,
Poland, June 3, 2010, p. 18-19.
9. Halberg F, Cornélissen G, Sothern
RB, Wallach LA, Halberg E, Ahlgren
A, Kuzel M, Radke A, Barbosa J,
Goetz F, Buckley J, Mandel J,
Schuman L, Haus E, Lakatua D,
Sackett L, Berg H, Wendt HW,
Kawasaki T, Ueno M, Uezono K,
Matsuoka M, Omae T, Tarquini B,
Cagnoni M, Garcia Sainz M, Perez
Vega E, Wilson D, Griffiths K,
Donati L, Tatti P, Vasta M,
Locatelli I, Camagna A, Lauro R,
Tritsch G, Wetterberg L.
International geographic studies of
oncological interest on
chronobiological variables. In:
Kaiser H, editor. Neoplasms --
Comparative Pathology of Growth in
Animals, Plants and Man. Baltimore:
Williams and Wilkins; 1981. p.
553-596.
10. Halberg F, Haus E, Cornélissen
G. From biologic rhythms to
chronomes relevant for nutrition.
In: Marriott BM, editor. Not Eating
Enough: Overcoming Underconsumption
of Military Operational Rations.
Washington DC: National Academy
Press; 1995. p. 361-372.
http://books.nap.edu/books/0309053412/html/361.html#pagetop
11. Arble DM, Bass J, Laposky AD,
Vitaterna MH, Turek FW. Circadian
timing of food intake contributes to
weight gain. Obesity 2009; 17:
2100-2102. doi:10.1038/oby.2009.264
12. Goetz FC, Bishop J, Halberg F,
Sothern RB, Brunning R, Senske B,
Greenberg B, Minors D, Stoney P,
Smith ID, Rosen GD, Cressey D, Haus
E, Apfelbaum M. Timing of single
daily meal influences relations
among human circadian rhythms in
urinary cyclic AMP and hemic
glucagon, insulin and iron.
Experientia (Basel) 1976; 32:
1081-1084.
13. Halberg F, Rosch P, Cornélissen
G. Acceptable conventional stress
test outcome may not dispel
indications of a sphygmochron. In:
Halberg F, Kenner T, Fiser B,
Siegelova J, eds. Proceedings,
Noninvasive Methods in Cardiology,
Brno, Czech Republic, July 7-10,
2009. (Dedicated to the 90th
Anniversary of Prof. Franz Halberg.)
p. 247-256.
http://web.fnusa.cz/files/kfdr2009/sbornik_2009.pdf
14. Halberg F. Protection by timing
treatment according to bodily
rhythms: an analogy to protection by
scrubbing before surgery.
Chronobiologia 1974; 1 (Suppl. 1):
27-68.
15. Nelson W, Cadotte L, Halberg F.
Circadian timing of single daily
"meal" affects survival of mice.
Proc Soc exp Biol (NY) 1973; 144:
766-769.
16. Cornélissen G, Kawasaki T,
Uezono K, Delea C, Halberg F. II:
Blood pressure rhythms and salt. Ann
Ist Super Sanità 1993; 29: 667-677.
Legends
Figure 1. Circadian rhythm detection
for cortisol, DHEA and melatonin
improves with length of time series.
© Halberg.
Figure 2. Cortisol and prolactin
rhythm detection greatly improves by
change to sampling at 20- rather
than at 100-minute intervals, i.e.,
with density of time series (9). ©
Halberg.
Figure 3. Circadian rhythm detection
for testosterone and estradiol
improves with length of time series
(but denser sampling is indicated).
© Halberg.
Figure 4A, top. Three young healthy
people on a diurnal-waking and
nocturnal-rest schedule lost weight
when they ate one daily meal of
2,000 calories within 1 hour of
awakening (breakfast-only) and all
gained weight when eating the same
2,000-calorie single daily meal only
12 hours after awakening
(dinner-only). From (10, 14). ©
Halberg.
Figure 4A, bottom. Access to food
restricted to one or the other
circadian stage on an alternating
light (L) and dark (D) schedule in
the mouse (without fat reserves and
with no chance to cuddle: 1C, i.e.,
1/cage, vs. 4C, 4/cage) kept in a
cool environment can make the
difference between survival and
death. From (15). © Halberg.
Figure 4B. Dinner-only leads to
relative body weight gain (as
compared to breakfast-only), whether
on a free-choice diet or on fixed
2,000 calories at each meal (on more
subjects as compared to 2A) (12).
The changes on breakfast-only
(B-only) vs. dinner-only (D-only)
are shown separately in this graph
and are summarized in 4C. © Halberg.
Figure 4C. Summary of relative body
weight loss on a single daily meal
consumed within 1 hour of awakening
(breakfast-only). From (10, 14). ©
Halberg.
Figure 4D. On a different topic,
i.e., whether to recommend sodium
restriction across the board for a
population as a whole, as done by
the state of New York, this figure
shows that thereby, in some cases,
blood pressure can be raised rather
than lowered with statistical
significance, ignoring "First do no
harm". From (16). © Halberg.
Table 1: Rhythm detection and
sampling requirements*
|
Hormone
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|
Interval
(hours)
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Percentage
of
analyses
yielding
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P≤0.01
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P≤0.05
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P≤0.10
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P≤0.50
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Cortisol
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24
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3
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9
|
26
|
80
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|
48
|
14
|
46
|
62
|
93
|
|
72
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39
|
69
|
79
|
98
|
|
96
|
56
|
88
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95
|
100
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|
168
|
93
|
100
|
100
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100
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DHEA
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24
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4
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20
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26
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81
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|
48
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35
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49
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62
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95
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72
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40
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67
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81
|
99
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|
96
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58
|
85
|
91
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100
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168
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92
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99
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100
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100
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Melatonin
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24
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1
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38
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61
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97
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48
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79
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91
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95
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100
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72
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92
|
98
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98
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100
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|
96
|
96
|
99
|
100
|
100
|
|
168
|
98
|
100
|
100
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100
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*From chronobiologic serial
sections, using a 24-hour increment.
P-values are from the zero-amplitude
(no-rhythm) test at a trial period
of 24 hours. Data (N=737) collected
during 133 days, include both
24.0-hour synchronized and
desynchronized states. Data
log-transformed prior to analysis to
render their distribution closer to
normality.
=================
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